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<div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="st1"> <!-- named anchor --> </a> <h5 class="section-title" id="d8978410e212">Introduction:</h5> <p dir="auto" id="d8978410e214"> <i>Candida albicans</i> biofilm formation is a significant contributor to antifungal resistance, necessitating new treatment strategies. <i>Annona muricata</i> Lin., a traditional herbal remedy, has shown promise in combating microbial infections. The purpose of this study was to assess the antibiofilm activity of the methanol extract of <i>A. muricata</i> leaves alone or with the addition of fluconazole against <i>C. albicans</i>. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="st2"> <!-- named anchor --> </a> <h5 class="section-title" id="d8978410e228">Methods:</h5> <p dir="auto" id="d8978410e230">Phytochemicals from the methanol extract were analyzed by LC-MS, the XTT assay was used for metabolic activity, and morphological characteristics were examined using scanning electron microscopy (SEM). Molecular docking screening of identified compounds in <i>A. muricata</i> methanol leaves extract against a Sap3 receptor (PDB: 2H6T) was also performed. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="st3"> <!-- named anchor --> </a> <h5 class="section-title" id="d8978410e236">Results:</h5> <p dir="auto" id="d8978410e238">The LC-MS analysis detected 17 possible phytochemicals. The methanol extract showed a dose-dependent inhibition of biofilm formation, with maximum inhibition of ~60% observed at 240 μg/ml, and inhibition by fluconazole increased from 32% to 76% as the concentration increased from 15 to 240 μg/ml. The combination of <i>A. muricata</i> and fluconazole increased the inhibition significantly, from 74% to 78% at 15 μg/ml to 240 μg/mL, respectively. SEM of control and treated <i>C. albicans</i> biofilms showed an altered morphology and loss of cell integrity by the combination, corroborating the findings. Plant phytochemicals also possess high binding affinity (−9.7 to 8.0 kcal/mol, respectively) for the Sap3 enzyme and may therefore have therapeutic potential against <i>C. albicans</i>. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="st4"> <!-- named anchor --> </a> <h5 class="section-title" id="d8978410e250">Conclusion:</h5> <p dir="auto" id="d8978410e252">Consequently, the findings indicate that compounds in the <i>A. muricata</i> methanol extract may function in concert with fluconazole at sub-inhibitory concentrations to suppress <i>C. albicans</i> biofilm formation. This finding paves the way for the formulation and development of antifungal treatment regimens that may limit the development of fluconazole resistance employing this plant part. </p> </div>